ZFIN ID: ZDB-PUB-200403-228
Nephrotoxic Effects in Zebrafish after Prolonged Exposure to Aristolochic Acid
Wang, X., Giusti, A., Ny, A., de Witte, P.A.
Date: 2020
Source: toxins   12(4): (Journal)
Registered Authors: de Witte, Peter
Keywords: aristolochic acid, chronic kidney disorder, fibrosis, nephrotoxicity, zebrafish
MeSH Terms:
  • Acute Kidney Injury/chemically induced*
  • Acute Kidney Injury/metabolism
  • Acute Kidney Injury/pathology
  • Animals
  • Animals, Genetically Modified
  • Aristolochic Acids/toxicity*
  • Collagen/metabolism
  • Fibrosis
  • Kidney/drug effects*
  • Kidney/metabolism
  • Kidney/pathology
  • Telomerase/deficiency
  • Telomerase/genetics
  • Time Factors
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish Proteins/deficiency
  • Zebrafish Proteins/genetics
PubMed: 32235450 Full text @ Toxins (Basel)
With the aim to explore the possibility to generate a zebrafish model of renal fibrosis, in this study the fibrogenic renal effect of aristolochic acid I (AAI) after immersion was assessed. This compound is highly nephrotoxic able to elicit renal fibrosis after exposure of rats and humans. Our results reveal that larval zebrafish at 15 days dpf (days post-fertilization) exposed for 8 days to 0.5 µM AAI showed clear signs of AKI (acute kidney injury). The damage resulted in the relative loss of the functional glomerular filtration barrier. Conversely, we did not observe any deposition of collagen, nor could we immunodetect α-SMA, a hallmark of myofibroblasts, in the tubules. In addition, no increase in gene expression of fibrogenesis biomarkers after whole animal RNA extraction was found. As zebrafish have a high capability for tissue regeneration possibly impeding fibrogenic processes, we also used a tert-/- zebrafish line exhibiting telomerase deficiency and impaired tissue homeostasis. AAI-treated tert-/- larvae displayed an increased sensitivity towards 0.5 µM AAI. Importantly, after AAI treatment a mild collagen deposition could be found in the tubules. The outcome implies that sustained AKI induced by nephrotoxic compounds combined with defective tert-/- stem cells can produce a fibrotic response.